Mutants of the de novo and salvage purine pathways are being studied in mammalian cells (CHO and L-cells), and in E. coli. Particular emphasis is being placed on regulation of the de novo pathway, and the interrelationship between salvage enzymes and the de novo pathway. Mutants, isolated as resistant to 2,6 diaminopurine, are analyzed for alterations in kinetic properties (Km,Ki), thermal stability, pH stability and presence of crossreacting material. To date both CRM plus and CRM minus mutants have been identified, as well as mutants with altered enzyme properties. In L-cells the mutation frequency to DAPR is abnormally high. This is being investigated. The enzyme APRT has been purified to homogeneity, and we are planning to do peptide analysis. Actinomycin D has been found to inhibit de novo purine biosynthesis. The effect of Actinomycin D on PRPP and PRPP synthesis is currently under study.